The immediate objective of this research project is to determine what factors regulate the activities and functions of the major ascending dopaminergic (DA) neurons in the rat brain. Biochemical indices of DA nerve activity will be determined in response to pharmacological and surgical manipulations in brain regions containing the cell bodies (ventromedial tegmentum (A10) and substantia nigra (A8 and 9)) and the terminals (striatum and nucleus accumbens) of nigrostriatal and mesolimbic DA neuronal systems. The influences of 1) the long striatonigral neuronal feedback loop and putative DA autoreceptors, 2) of 5-hydroxytryptamine neurons, and iii) of putative cerebellonigral neurons will be determined on the regulation of nigrostriatal and mesolimbic systems. This will be accomplished by the application of microinjections of drugs to the regions of the DA cell bodies and terminals, and by determining the effects of lesions to afferent neuronal systems that are believed to modulate the DA neurons.